Autogeny in Aedes aegypti

埃及伊蚊的自体繁殖

• 批准号: 8020955
• 负责人: DAVID W SEVERSON
• 金额: $ 11.14万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8020955
• 关键词: Address; Aedes; Automobile Driving; Behavior; Biochemical Pathway; Biology; Blood; Candidate Disease Gene; Cessation of life; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 3; Complex; Culicidae; Data; Deltastab; Dengue; Dengue Virus; Developed Countries; Developing Countries; Development; Disease; Disease Outbreaks; Drug resistance; Engineering; Epidemic; Event; Evolution; Experimental Designs; Feeding behaviors; Female; Fingerprint; Fostering; Foundations; Future; Genes; Genetic; Genetic Markers; Genome; Genomics; Goals; Health; Human; Incidence; Individual; Insecticide Resistance; Institutes; Investigation; Knowledge; Libraries; Microsatellite Repeats; Modeling; Molecular; Molecular Genetics; Mosquito Control; Mosquito-borne infectious disease; Outcome; Ovarian Cycles; Oviposition; Parasites; Phenotype; Population; Population Biology; Positioning Attribute; Production; Protocols documentation; Quantitative Genetics; Quantitative Trait Loci; Reporting; Research; Resolution; Services; Shotgun Sequence Assembly; Single Nucleotide Polymorphism; Single-Stranded Conformational Polymorphism; Techniques; Transgenes; Travel; Universities; Vaccines; Vitellogenesis; Whole-Genome Shotgun Sequencing; base; disorder control; disorder prevention; egg; genetic analysis; genome sequencing; genome wide association study; novel; pathogen; physical mapping; positional cloning; prevent; programs; public health relevance; research study; tool; trait; transmission process; vaccine development; vector

DESCRIPTION (provided by applicant): Mosquito-borne diseases present an increasing global human health threat. These diseases reflect a significant resurgence in most developing countries, and also are emerging as clear threats for epidemic outbreaks in developed countries. Many factors contribute to the inability to date to prevent or control these diseases including poor progress in vaccine development, emergence of insecticide resistance in mosquito populations, drug resistance among parasite populations, lack of support in many developing countries for mosquito control programs, and increased global travel. This proposal seeks to initiate investigations on the autogeny trait observed in many mosquito species examined to date; autogenous females are able to produce an egg batch without the typical need for a blood meal as is typical with most female mosquitoes. Understanding the fundamental biology of mosquito populations, and particularly aspects of vitellogenesis, is critical to proposed efforts to utilize novel genetic approaches for controlling mosquito-borne diseases. At present, no knowledge exists on the molecular determinants of autogeny in any mosquito species. The focus of this proposal is the detailed genetic investigation of autogeny in Aedes aegypti as the model mosquito species for rapidly and efficiently uncovering the genetic basis for autogeny. Our long-term goals for these efforts are to eventually uncover genetic mechanisms likely common to autogeny determination in most if not all mosquito species. Aedes aegypti is the primary global vector for dengue virus. Dengue is a threat to >2.5 billion people, with an annual incidence of ~50 million cases and ~500,000 cases of DHF/DSS resulting in ~24,000 deaths per year. The objectives of this proposal are based on the general hypothesis that genes associated with the autogeny phenotype can be identified and isolated by positional cloning techniques. The proposed research will define a strong foundation toward the eventual detailed investigations of the genes determining autogeny and the knowledge obtained from the detailed understanding of the associated biochemical pathways will increase our basic understanding of vitellogenesis in mosquitoes which has implications for predicting vectorial capacity among mosquito populations. This could have several potential applications including transgene constructs that promote altered and disease limiting behaviors that significantly reduce vectorial capacity, development of targeted biopesticides, or identification of biologically relevant antagonists that disrupt behaviors critical to pathogen transmission or survival. The research plan builds upon and enhances the information obtained from the Ae. aegypti genome project to develop the necessary tools toward the eventual complete elucidation of these gene relationships and their phenotypic outcome. The specific aims of the project are to: 1) perform fine-scale genetic mapping to identify regions containing genes that determine the autogeny phenotype in Aedes aegypti and 2) conduct high-resolution, fine-scale physical mapping of an Aedes aegypti BAC library. PUBLIC HEALTH RELEVANCE: Aedes aegypti is the primary vector for dengue virus. No vaccines are available and disease prevention is largely dependent on avoiding contact with infected mosquitoes. The proposed research will provide valuable new information on the biology of this mosquito relating to the ability of some females to produce eggs without obtaining a blood meal.

描述(申请人提供)：蚊媒疾病对全球人类健康构成日益严重的威胁。这些疾病反映了大多数发展中国家的显著死灰复燃，也正在成为发达国家疫情暴发的明显威胁。许多因素导致迄今无法预防或控制这些疾病，包括疫苗开发进展缓慢、蚊子种群出现杀虫剂抗药性、寄生虫种群出现抗药性、许多发展中国家缺乏对蚊子控制项目的支持以及全球旅行增加。这项建议旨在启动对迄今为止在许多被检查的蚊子物种中观察到的自生特征的调查；自体雌性蚊子能够产生一批卵子，而不需要像大多数雌性蚊子那样典型地需要血餐。了解蚊子种群的基本生物学，特别是卵黄发生的方面，对于拟议的利用新的遗传方法控制蚊媒疾病的努力至关重要。目前，还没有关于任何蚊子物种自交的分子决定因素的知识。这项建议的重点是对埃及伊蚊的自体繁殖进行详细的遗传学研究，以期快速有效地揭示自体繁殖的遗传基础。我们这些努力的长期目标是最终发现在大多数蚊子物种(如果不是所有蚊子物种的话)中可能共同决定自体遗传的遗传机制。埃及伊蚊是登革热病毒的主要全球传播媒介。登革热对25亿人构成威胁，每年约有5000万例登革热病例和约50万例DHF/DSS病例，每年导致约24000人死亡。这一建议的目的是基于这样一个普遍假设，即与自体表型相关的基因可以通过位置克隆技术来识别和分离。这项拟议的研究将为最终详细研究决定自体发生的基因奠定坚实的基础，从相关生化途径的详细了解中获得的知识将增加我们对蚊子卵黄发生的基本理解，这对预测蚊子种群的媒介能力具有重要意义。这可能有几个潜在的应用，包括促进显著降低媒介能力的改变和疾病限制行为的转基因构建，开发靶向生物杀虫剂，或者识别生物相关的拮抗剂，破坏对病原体传播或生存至关重要的行为。研究计划建立在从原子能机构获得的信息的基础上，并加强了这些信息。埃及埃及人基因组计划，以开发必要的工具，最终完全阐明这些基因关系及其表型结果。该项目的具体目标是：1)进行精细的遗传作图，以确定含有决定埃及伊蚊自生表型的基因的区域；2)对埃及伊蚊BAC文库进行高分辨率、精细的物理作图。 公共卫生相关性：埃及伊蚊是登革热病毒的主要传播媒介。没有疫苗可用，疾病预防在很大程度上依赖于避免接触受感染的蚊子。这项拟议的研究将为这种蚊子的生物学提供有价值的新信息，这些信息与一些雌性蚊子在不获取血餐的情况下产卵的能力有关。